Left ventricular remodeling leads to heart failure in mice with cardiac‐specific overexpression of VEGF‐B₁₆₇: echocardiography and magnetic resonance imaging study

Abstract

Cardiac‐specific overexpression of vascular endothelial growth factor (VEGF)‐B167 is known to induce left ventricular hypertrophy due to altered lipid metabolism, in which ceramides accumulate to the heart and cause mitochondrial damage. The aim of this study was to evaluate and compare different imaging methods to find the most sensitive way to diagnose at early stage the progressive left ventricular remodeling leading to heart failure. Echocardiography and cardiovascular magnetic resonance imaging were compared for imaging the hearts of transgenic mice with cardiac‐specific overexpression of VEGF‐B167 and wild‐type mice from 5 to 14 months of age at several time points. Disease progression was verified by molecular biology methods and histology. We showed that left ventricular remodeling is already ongoing at the age of 5 months in transgenic mice leading to heart failure by the age of 14 months. Measurements from echocardiography and cardiovascular magnetic resonance imaging revealed similar changes in cardiac structure and function in the transgenic mice. Changes in histology, gene expressions, and electrocardiography supported the progression of left ventricular hypertrophy. Longitudinal relaxation time in rotating frame (T1ρ) in cardiovascular magnetic resonance imaging could be suitable for detecting severe fibrosis in the heart. We conclude that cardiac‐specific overexpression of VEGF‐B167 leads to left ventricular remodeling at early age and is a suitable model to study heart failure development with different imaging methods.

Guidelines for measuring cardiac physiology in mice

“…While many clinical studies have compared data obtained from both echocardiography and MRI in the same patients ( 93 , 94 ), experimental models comparing both modalities are limited. Experimental mouse models comparing the use of echocardiography with MRI noted good correlation in measures of volume and physiology ( 108 ). With the comparison of changes in cardiac structure, MRI was better at detecting moderate to severe diffuse myocardial fibrosis.…”

New cardiac magnetic resonance imaging modalities aid in the detection of myocardial fibrosis

“…In this study, Lottonen‐Raikaslehto and colleagues (Lottonen‐Raikaslehto et al ) demonstrate that the cardiac magnetic resonance (CMR) imaging modality, T1 longitudinal relaxation in the rotating frame (known as T 1 ρ ), can be potentially used as a sensitive method to detect diffuse fibrosis in the heart, indicating that this technique may be a valuable addition to the arsenal of clinical imaging methods for cardiac diseases such as HF. Although traditional 2D echocardiography remains the initial and most frequently utilized imaging exam for HF, it continues to suffer from the major limitation of user dependence (Marwick and Schwaiger ; Paterson et al.…”

“…The authors have focused on T 1 ρ imaging as a method that might potentially aid in the diagnosis of cardiac failure in earlier stages of the disease, prior to the manifestations of impaired ventricular function (Lottonen‐Raikaslehto et al ). Indeed, a very promising outcome of a noninvasive method to detect diffuse fibrosis within the myocardium would be in the identification of subclinical states of LV hypertrophic (LVH) remodeling.…”

“…(Lottonen‐Raikaslehto et al. ) have characterized remodeling of the VEGF‐B 167 mouse hearts with gene expression studies and ECG measurements. LVH phenotype was demonstrated by increased expression of ANP and decreased expression of cTnT at 5, 10, and 14 months of age in VEGF‐B 167 mice compared with WT controls.…”

Evaluation of the effects of different treatment modalities on angiogenesis in heart failure patients with reduced/mid-range ejection fraction via VEGF and sVEGFR-1

“… 9 - 11 The importance of VEGF was shown previously in animal studies as a mediator for inducing new blood vessels with regard to cardiac remodeling. 12 Patel et al 13 showed that VEGF levels did not differ among varying degrees of LV systolic functions or did not correlate with levels of EF. In this study, VEGF levels were not found to be significantly higher in HFrEF and HFmrEF patients and no significant correlation was detected with echocardiographic findings in patients and control groups, which was compatible with previous studies.…”